1 RBCIAMB | n.50 | dez 2018 | 1-25 Fernanda Majolo PhD, Pontifícia Universidade Católica do Rio Grande do Sul, PUC-RS – Porto Alegre (RS), Brazil. Claudete Rempel Doutora, Universidade do Vale do Taquari, Univates – Lajeado (RS), Brazil. Corresponding address: Fernanda Majolo – Programa de Pós-Graduação em Medicina e Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul – Avenida Ipiranga, 6681 – Partenon – CEP 90610-000 – Porto Alegre (RS), Brasil. E-mail: fernanda.majolo@acad.pucrs.br Received on: 07/10/2018 Accepted on: 12/05/2018 ABSTRACT Brazil is the third largest market and the eighth largest consumer of pesticides per hectare in the world, with herbicides and insecticides accounting for 60% of the products traded in the country. The use of pesticides has increased worldwide in the last decades, which may represent a risk for several diseases in humans, including cancer. Although in Brazil the research on the impact of the use of pesticides on human health has grown in recent years, it is still insufficient to really know the real dimension of health damage caused mainly by occupational and food exposure, due to the intensive use of pesticides. This article aims to review the use of pesticides by rural workers in Brazil, highlighting the importance of preventive measures for their health. Keywords: health disorders; occupational health; cancer; genotoxicity; oxidative stress; strategies. RESUMO O Brasil é o terceiro maior mercado e o oitavo maior consumidor de agrotóxicos por hectare do mundo, com herbicidas e inseticidas correspondendo a 60% dos produtos comercializados no país. O uso de agrotóxicos tem aumentado em todo o mundo nas últimas décadas, o que pode representar um risco para diversas doenças em humanos, incluindo o câncer. Embora, no Brasil, a pesquisa sobre o impacto do uso de agrotóxicos na saúde humana tenha crescido nos últimos anos, ainda é insuficiente para de fato conhecer a real dimensão dos danos à saúde, causados principalmente pela exposição ocupacional e alimentar, em virtude da utilização de agrotóxicos. Esta revisão tem por objetivo destacar o uso de pesticidas por trabalhadores rurais no Brasil, evidenciando a importância de medidas preventivas para a saúde do trabalhador. Palavras-chave: transtornos de saúde; saúde ocupacional; câncer; genotoxicidade; estresse oxidativo; estratégias. DOI: 10.5327/Z2176-947820180357 IMPACT OF THE USE OF PESTICIDES BY RURAL WORKERS IN BRAZIL IMPACTO DO USO DE AGROTÓXICOS POR TRABALHADORES RURAIS NO BRASIL http://orcid.org/0000-0002-7955-078X http://orcid.org/0000-0001-8573-0237 Majolo, F.; Rempel, C. 2 RBCIAMB | n.50 | dez 2018 | 1-25 INTRODUCTION Pesticides, according to the World Health Organization (WHO, 2008), is any substance capable of controlling a pest that can have consequences for both the popula- tion and the environment. Among the countries with agricultural power involving the consumption of her- bicides, fungicides and agricultural insecticides, Brazil ranks first in the Latin American and Caribbean News- letter, dated 23 of April 2011 (STÉDILE, 2012; NEVES, 2017). In Brazil, the diversity of agrochemicals is big, about 300 active principles in more than 2 thousand commercial formulations (NEVES, 2017). Humans are often their final recipients, and they can be found in the soil, water, air, in animals and vegetables, being thus considered with great capacity of dispersion (NEVES, 2017). Different symptoms are caused by pesticide poisoning, mainly among farm- ers, and may even make them stop working and having to look for another type of profession. Among the symp- toms, we can highlight anemia, headache, dysthymia, de- creased immune defenses, sexual impotence, insomnia, changes in arterial depression and behavioral disorders (LEVIGARD; ROZEMBERG, 2001; SOUZA et al., 2011). With its effect based on insect neurotoxicity, dichlo- rodiphenyltrichloroethane (DDT), is a widely known pesticide, mainly because it is sold at a low cost and can act for several years (STOPELLI; MAGALHÃES, 2005). However, it has some limitations: insects have devel- oped resistance to it and experiments with animals showed their carcinogenicity (SMITH; GANGOLLI, 2002; STOPELLI; MAGALHÃES, 2005). Already in humans, high concentrations of Dieldrin in the blood, for example, have a greater amount of thyroid stimulating hormone (TSH), presenting hypothyroidism. Therefore, this pes- ticide and other organochlorines act as neurotoxicants, as well as in the endocrine function ( RATHORE et al., 2002; STOPELLI & MAGALHÃES, 2005). Many studies have presented promising results and made important conclusions beyond the use of pesti- cides by rural workers, allowing a better understanding of the consequences of its use. Due to the accumulated knowledge, we aimed at conducting a survey on the most important and promising researches on the use of pesticides by rural workers in Brazil until now. THE BRAZILIAN SITUATION Because of agricultural practices in the country, around the 1960s the whole scenario underwent modifica- tions leading to a record consumption of agrochemi- cals and a chemical-dependent context of food produc- tion (ABREU; ALONZO, 2014; JACOBSON et al., 2009). In the global context, since 2008 Brazil has become the largest consumer of pesticides (CARNEIRO et al., 2012; AUGUSTO et al., 2012; RIGOTTO et al., 2012), standing out as the world’s largest agricultural producer. Brazil shows growth rates of 10% per year (AGRONEWS, 2014; BRASIL, 2015; GONÇALVES, 2016) and exports food to 180 countries, being the world’s leading exporter of soybeans in grains, sugar, coffee, orange juice, beef and chicken (BRASIL, 2013; GONÇALVES, 2016). According to IBAMA (2002), the states of Mato Grosso, São Paulo, Paraná, Rio Grande do Sul, Goiás, Minas Gerais, Bahia and Mato Grosso do Sul are the main consumer states of agrochemicals (Figure 1). Especially for the rural worker, along with the evolution of techniques and the use of agricultural inputs, there have been harmful changes in health, mainly related to the loads, ways of working and risks incorporated into these new activities (STOPPELLI & MAGALHÃES, 2005). These risks involve both acute intoxications, with the on- set of symptoms fast after excessive exposure, including weakness, vomiting, nausea, seizures, muscle contrac- tions, headaches, difficulty breathing, nasal bleeding and fainting, as well as chronic intoxication. In these, the symptoms are late after months or years, caused by small or moderate exposure to toxic products or multi- ple products. This type of exposure causes irreversible damage, such as paralysis and neoplasia (PERES, 1999; STOPPELLI & MAGALHÃES, 2005), contact dermatitis, renal and hepatic lesions, delayed neurotoxic effects, chromosomal abnormalities, Parkinson’s disease, can- cers and teratogens (WILSON; OTSUKI, 2004; STOPPELLI & MAGALHÃES, 2005). Table 1 shows the main studies carried out to date specifically related to the exposure of the rural worker to pesticides in Brazil. Electronic da- tabases were collected from PUBMED and “Portal de Periódicos” from CAPES/MEC (Coordenação de Aper- feiçoamento de Pessoal de Nível Superior/ Ministério Impact of the use of pesticides by rural workers in Brazil 3 RBCIAMB | n.50 | dez 2018 | 1-25 Source: IBAMA, 2018. Figure 1 – Federation sales of agrochemicals by Unit in 2017. *No definition: sum of marketed quantities whose companies are not able to specify the terri- torial distribution of sales, since it is an activity carried out by third parties. To ns o f a c� ve in gr ed ie nt 95,000 70,000 45,000 20,000 15,000 12,500 10,000 7,500 5,000 2,500 0 A C A M A P PA RO R R TO D F G O M S M T A L BA C E M A PB P E PI RN S E ES M G RJ SP PR R S SC N o de fin i� on Continue... Table 1 – Update of the main publications related to the use of pesticides by rural workers in Brazil. State Target Major findings Methodology Reference Year HEALTH DISORDERS AND OCCUPATIONAL HEALTH SE High frequency hearing loss; Noise exposure; Quality of life Pure-tone audiometry, distortion product otoacoustic emissions, and high-frequency audiometry tests were performed. This report is unusual because of the short time of exposure to noise and pesticides and the hearing loss found, indicating a synergy between those agents. Pure-tone audiometry, distortion product otoacoustic emissions, and high-frequency audiometry tests. Sena et al. 2018 ES Beck Depression Inventory-II (BDI-II); Depressive Symptoms; Mental Health Pesticide exposure, tobacco use, poor self-perceived health and the presence of chronic disease contribute as risk factors for the appearance of depressive symptoms at a level above ups and downs considered normal in the BDI-II. Questionnaire Conti et al. 2018 Majolo, F.; Rempel, C. 4 RBCIAMB | n.50 | dez 2018 | 1-25 State Target Major findings Methodology Reference Year SC Artificial Targets; Tractor Cabins; Exposure Evaluation; Fenitrothion; Crop Pulverization Sealed cabin minimized the exposure of the operator to the pesticides, since all samples analyzed showed fenitrothion values below the limit of detection. Ultrasonic extraction Barcellos et al. 2016 RS Agrochemicals; Work Environment; Practical Nursing. Rural workers who apply pesticides present a higher prevalence of dermatological alterations. Questionnaire Cezar-Vaz et al. 2016 RS Wheezing; Asthma; Tobacco; Rural Health; Prevalence Pesticides, dusts exposure, and green tobacco sickness were risk factors for wheezing. Questionnaire Fiori et al. 2015 Brazilian micro- region Suicide Suicide rates have increased in middle age (35–64 years) and younger men (15–34 years). Micro-regions with a higher use of pesticides showed higher rates of suicides. Pesticide poisoning effect on suicide rates was stronger than use of pesticide. Reinforces the hypothesis that pesticide use and pesticide poisoning increase the suicide rates. Crude suicide rates of a 15- year time series (1996–2010) were examined, followed by an ecological study using age-standardized suicide rates for the period 2006–2010. Faria et al. 2014a MG Health and Epidemiological Surveillance; Health Policies The conclusion is the pressing need to develop a model for sustainable agriculture, healthy, free of pesticides and that organized society and responsible institutions must undertake actions that meet the needs of the people who work in the farms or consume agricultural products harvested there, especially controlling risks and consequences that can and must be avoided. Questionnaire Nasrala Neto, Lacaz and Pignati 2014 RS Poisoning; Mental disorders Reinforces the evidence of the association between pesticide poisoning and mental health disorders. It also points to increased risk of minor psychiatric disorders from low socioeconomic status, dermal pesticide exposure and exposure to organophosphates. Reveals intense nicotine exposure as a risk for tobacco farmers’ mental health. Characterizing economic indicators of the farms, socio- demographic factors, lifestyle habits and occupational exposures. Faria et al. 2014b Continue... Table 1 – Continuation. Impact of the use of pesticides by rural workers in Brazil 5 RBCIAMB | n.50 | dez 2018 | 1-25 State Target Major findings Methodology Reference Year SE Rural Population; Quality of life Agricultural workers users of pesticides showed the worst levels of quality of life when compared to those who have not handled them. The use of pesticides and their toxicity class interfered in a most striking way in the classification of hearing loss presented by this group. Audiological evaluation Sena, Vargas and Oliveira 2013 RJ Risk Perception; Risk Communication; Defensive Strategies; Community-Based Participatory Research Risk perceptions and work practices are strongly influenced by local cultural patterns and, therefore, must be taken into account when developing effective intervention strategies, including risk communication initiatives. Questionnaire Peres et al. 2013 RJ Small holders; Environment Human health Do not confirm that the farmers’ apparent careless handling of pesticides is linked to an intentional disregard for intoxication risk. The results point to a more complex set of explanatory variables that include: labor scarcity, inadequacy of protective gear, mixing practices and limited educational effectiveness of labeling standards. Questionnaire Pedlowskia et al. 2012 DF Knowledge, attitudes, and practices study; Acetylcholinesterase; Butyrylcholinesterase Although most farmers were aware that pesticides can harm their health, many still use PPDs in an inappropriate manner, or not at all, during pesticide handling. Inhibition of ChE activity during the exposure period for some farmers was higher than the safe, indicating that they might be at risk by the exposure to pesticides during their agricultural activities. Questionnaire and Blood sample Pasiani et al. 2012 RJ Hearing; Auditory Perception; Adverse Effects. Workers exposed to pesticide performed below-average on Temporal Auditory Processing tests. There was association between the index of exposure to pesticides and worse performance in Temporal Auditory Processing tests, suggesting that pesticides may be harmful to central auditory pathways. Questionnaire, meatoscopy, basic audiological evaluation and temporal auditory processing tests. Bazilio et al. 2012 Continue... Table 1 – Continuation. Majolo, F.; Rempel, C. 6 RBCIAMB | n.50 | dez 2018 | 1-25 State Target Major findings Methodology Reference Year RJ Health Indicators; Rural Labor; Public Health The volume of the determinants identified in the DPSEEA Matrix are related to deficiencies in actions for monitoring and surveillance of pesticide use, as well as the lack of technical assistance provided by the Public Sector. DPSEEA model (WHO) based on analysis of official public documents. Araújo-Pinto, Peres and Moreira 2012 PR Poisoning; Economy; Health expenditures Society, especially the population most affected by agrochemicals, would benefit if the risks of acute intoxication associated with the current model of agricultural production were recognized and eliminated. Information obtained from Pesquisa de Previsão de Safras from 1998 to 1999. Soares and Porto 2012 RJ Mortality rates; Hospitalization rates attributable to suicide attempts; Sales of pesticides Pesticide exposure may indeed increase the risk of suicide frequency, especially among agricultural workers. Data on mortality rates, hospitalization rates attributable to suicide attempts, and data on sales of pesticides. Meyer et al. 2010 MG Rural Settlements; Social Conditions; Family Health; Rural Health; Food Security; Rural Population Health; Landless Worker Movment. The view held by families from the Landless Rural Workers’ Movement was that as they belonged to the Movement and were better organized, their health was better than the temporary rural workers’. The conservative modernization of rural Brazil has led to worse conditions for temporary rural workers, while Agrarian Reform has allowed for a better quality of life and improved health conditions among families in the areas under study. Questionnaire Carneiro et al. 2008 RJ Environmental Pollution Discusses several pesticide-related implications for human health and the environment in the mountainous region of the State of Rio de Janeiro, an important farming center. The article presents the results of the research in the area, identifying possible determinants of the current situation and some of the main challenges in dealing with the problem. Survey Peres and Moreira 2007 Continue... Table 1 – Continuation. Impact of the use of pesticides by rural workers in Brazil 7 RBCIAMB | n.50 | dez 2018 | 1-25 State Target Major findings Methodology Reference Year RJ Intoxication; Multiple Application; Delayed-Neuropathy; Organophosphate Pesticides These results indicate recurrent multiple overexposures to high concentrations of different chemicals, with serious damage to vital functions, especially considering their young age (average 35 ± 11 years old) and the productive period in their lifetime. Questionnaire, biological sample collection for toxicology analysis and clinical – general and neurological – assessment. Araújo et al. 2007 RJ Neurobehavioral While a few Behavioral Assessment and Research System (BARS) performance measures suggested behavioral impairments for the rural versus the urban participants, a stronger and more consistent association between BARS measures (especially impairment of tapping, digit span, and selective attention) and level of exposure to pesticides was noted when the exposure index was input into a multiple linear regression analysis. Exposure seemed to be especially strong for the youngest participants (10-11 years old). Questionnaire, Behavioral Assessment and Research System (BARS) to assess their performance. Eckerman et al. 2007 MS Knowledge, Attitude and Practices (KAP) survey About 92% of the interviewees had worked directly with pesticides and 59.6% reported typical intoxication symptoms. Only 44.3%, however, believe they had been intoxicated. A significant correlation was found between hand washing after pesticide application and reporting symptoms. Less than 20% used masks, impermeable clothes, or gloves during pesticide application. Questionnaire Recena et al. 2006 RJ Risk Perception; Risk Communication; Women’s Health Results showed that the inclusion of risk-perception studies in the development of educative and risk-communication campaigns is very important, linking research to action. Questionnaire Peres et al. 2006 Continue... Table 1 – Continuation. Majolo, F.; Rempel, C. 8 RBCIAMB | n.50 | dez 2018 | 1-25 State Target Major findings Methodology Reference Year RJ Risk; Rural Population Results pointed to the importance of risk perception analysis in the process of developing strategies of intervention in rural areas, especially in policies and educational risk communication campaigns. Questionnaire and assessment of local work processes. Peres, Rozemberg and De Lucca 2005 MS Suicide; Poisoning Poisonings occurred mostly from October to March and the organophosphate insecticides monocrotophos and methamidophos were the main pesticides involved. Reports from 1992 to 2002, using data from the Integrated Center for Toxicological Surveillance under the State Health Department. Pires, Caldas and Recena 2005 RJ Agriculture; Pesticide Exposure Highlights health professionals’ discourse in relation to the association between “nervousness” and pesticides. The authors discuss factors related to this perception and make several suggestions for future research. Questionnaire Levigard e Rozemberg 2004 RS Pesticide Exposure; Incidence Based on Poison regression, applying pesticide, reentering crop fields after spraying and working with pesticides in more than one farm were the types of exposure that presented a positive correlation with pesticide poisoning. Questionnaire Faria et al. 2004 MG Risk Factors; Poisoning; Rural Health The results emphasize the high level of health risk associated to pesticide use among rural workers. Questionnaire. Data obtained through the Jorge Duprat Figueiredo Foundation for Workers’ Safety and Occupational Medicine. Soares, Almeida and Moro 2003 MG Economic Assessment Points to the need for an extensive investigation on the real benefits of pesticide use and its consequences for the environment and health in Brazil. Data were obtained from the Fundacentro Ministry of Work agency for the years 1991-2000 Soares, Moro and Almeida 2002 Continue... Table 1 – Continuation. Impact of the use of pesticides by rural workers in Brazil 9 RBCIAMB | n.50 | dez 2018 | 1-25 State Target Major findings Methodology Reference Year RJ Communication; Health Education; Interview; Communication and Health. This study pointed out to the historical misinformation on pesticides in rural areas. Questionnaire Peres et al. 2001 RJ Insecticides; Organophosphate; Poisoning; Socioeconomic Factors; Carbamates; Cholinesterase Inhibitors; Blood. A result of 3.0 % was found for the BChE values, and 41.8 %, according to AChE. Individuals with at least one positive enzymatic indicator result were considered as “intoxicated”. When these data were compared to the social-economic and pesticides use factors, the importance of the educational level in the prevalence of intoxication was highlighted. AChE and BChE activities Oliveira-Silva et al. 2001 PE Tomatoes; Environment Impacts; Health Surveillance. There is a lack of effective policies to protect the health of rural workers who must deal with pesticides and the environment which has already been severely damaged. Questionnaire Araújo, Nogueira and Augusto 2000 RS Pesticide Poisoning; Occupational Accidents; Agriculture The high prevalence of health problems identified in the study calls attention to the need for measures to promote and protect rural workers’ health. Questionnaire Faria et al. 2000 RS Mental Health; Poisoning; Educational Status. The results call attention to the problem’s dimension and to the importance of adopting new policies to protect farm workers’ mental health. Questionnaire Faria et al. 1999 RJ Ddt; Dieldrin; Occupational Exposure Serum concentrations of organochlorine pesticides found in this study are comparable to the levels reported for the non- occupationally exposed population in Brazil and elsewhere. Blood samples, Serum levels of organochlorine pesticides measured. Paumgartten et al. 1998 BA Occupational and Environmental Exposure Rural workers and public health authorities must become aware of the importance of protective equipment, periodic health examinations and reduced environmental pollution in order to lessen occupational risks of field workers and promote improved conditions of life for the rural population. Parameters of biochemistry, hematology, and organochlorine insecticide residues in the blood. Carvalho 1991 Continue... Table 1 – Continuation. Majolo, F.; Rempel, C. 10 RBCIAMB | n.50 | dez 2018 | 1-25 State Target Major findings Methodology Reference Year SP CNS Magnese Intoxication Occupational exposure to pesticides containing Mn is a possible source of Mn intoxication of the CNS. Mn intoxication Ferraz et al. 1988 CANCER, GENOTOXICITY, DNA DAMAGE, OXIDATIVE STRESS SP Machine Learning; Genotoxicity Micronucleus; Smoking; Agriculture Exposing agricultural workers to pesticides and/or tobacco had genotoxic potential, but concomitant exposure to xenobiotics did not lead to additive or potentiating effects. Oral mucosa cells, cytogeneticanalysis Tomiazzi et al. 2018 SC DNA Damage; Oxidative Stress Exposed individuals, participants of this study, are more subject to suffer genetic damage and, consequently, more susceptible to diseases resulting from such damages Blood samples, comet assay and the cytokinesis- block micronucleus technique and thiobarbituric acid reactive substance and catalase activity. Hilgert Jacobsen- Pereira et al. 2018 MG Genotoxicity Test; Bioindicators and Clinical Evaluation The group exposed to organophosphates presented significant changes in all these parameters compared to the control group and showed significant changes in budding, condensed chromatin and karyolytic cells compared to the group non- exposed to organophosphates. Data from clinical evaluation showed significant changes in the central nervous, respiratory and auditory systems. Blood, urine and buccal samples, activities of cholinesterases, the levels of urinary dialkyl phosphates, genotoxicity data, from a cytome assay. Silvério et al. 2017 RS Skin Neoplasms; Occupational Risks; Oncology Nursing; Clinical Competence; Health Communication This study’s results allowed to clarify the combination of clinical knowledge and risk communication regarding skin cancer to rural workers. Observational- exploratory study Cezar-Vaz et al. 2015 RS Oxidative stress, TBARS, protein carbonyls. The results demonstrated a change in the oxidative status of rural workers compared to the control group, mainly by possible inhibition of AChE activity and the occurrence of oxidative stress without showing changes in biochemical parameters. Questionnaire and blood sample Murussi et al. 2014 Continue... Table 1 – Continuation. Impact of the use of pesticides by rural workers in Brazil 11 RBCIAMB | n.50 | dez 2018 | 1-25 State Target Major findings Methodology Reference Year RJ Brain Cancer; Age- Period-Cohort; Agriculture; Trend There is an increasing trend in brain cancer mortality rates in the rural Serrana Region in Brazil. At the ecological level, different environmental factors, especially the use of pesticides, may explain regional disparities in the mortality patterns from brain cancers. Descriptive study examined brain cancer mortality who died between 1996 and 2010. Miranda Filho et al. 2014 GO Occupational Exposure; DNA Damage; MN Comet Assay Occupational exposure to pesticides could cause genome damage in somatic cells, representing a potential health risk to rural workers that constantly deal with agrochemicals without adequate personal protection equipment. Micronucleus and the comet assay. Khayat et al. 2013 GO Polymorphism GST; Biomarkers The authors could not associate a null GSTT1 or null GSTM1 polymorphisms or both to intoxication events caused by pesticides, but instead they presented the importance of using Personal Protection Equipment to prevent such harm. Blood sample Godoy et al. 2014 CE Biomonitoring; Human Lymphocytes; Comet Assay; Chromosomal Aberrations Damages caused by pesticides in our study area were not great enough to induce permanent mutations or to interfere with mitotic apparatus formation; minimal pesticide damages could have undergone cellular repair, explaining the absence of structural and numerical chromosome aberration. Alkaline comet assay and the chromosome aberration test. Paiva et al. 2011 PE and AL Carcinogenesis; Analysis of Principal Components Both endosulfan and its metabolites are electrophilic and have carcinogenic potential. Electronic paramenters (Electron affinity, dipole moments, electrostatic attaction, formation heat and permeability of the cell membrane). Bedor et al. 2010 Continue... Table 1 – Continuation. Majolo, F.; Rempel, C. 12 RBCIAMB | n.50 | dez 2018 | 1-25 State Target Major findings Methodology Reference Year SP Cancer; Agriculture; Cancers of the skin and digestive system were the most prevalent. Database containing records of Amaral Carvalho Hospital. De Brito Sá Stopelli and Crestana 2005 RJ Mortality; Cancer; Ecological analysis Agricultural workers 30–49 years old showed higher, but not statistically significant, mortality by stomach, esophagus, liver, testis, and prostate cancer, and soft-tissue sarcoma in the period of 1979–1988, and by testis and penis cancer, leukemia, and soft- tissue sarcoma in the period of 1989–1998. National Mortality Information System between 1979 and 1998 Meyer et al. 2003 SP Chromosome Aberrations; Toxicology; Contamination. Although workers used protection against the pesticide’s fog, the results revealed that they were contaminated with the pesticides. Toxicological dosages of copper, zinc and manganese, hepatic enzyme dosage and acetylcholinesterase activity Brega et al. 1998 REPRODUCTIVE HORMONES, SPERM QUALITY RS Agricultural Workers; Anogenital Distance; Fungicides; Herbicides; Reproductive Hormones; Sperm Quality Chronic occupational exposure to modern pesticides, particularly herbicides and fungicides, may adversely affect semen quality in young male farmers, potentially leading to poorer morphology. Also, exposure to agricultural pesticides may acutely increase prolactin and chronically alter sex hormone levels acting at the pituitary level through prolactin and LH suppression, hampering compensatory responses to testicular dysfunction. Reproductive hormones, semen quality, and genital measures Cremonese et al. 2017 RJ Endocrine disruptors; Estrogenic compounds; Organochlorines; Testosterone Seem to support the known capacity of organochlorines pesticides to exert estrogenic and anti-androgenic activity, affecting sex hormone systems through mechanisms of action that may be different for each individual compound. Interviews and blood sample. Freire et al. 2014 ES: Espírito Santo; SP: São Paulo; RJ: Rio de Janeiro; PR: Paraná; RS: Rio Grande do Sul; MG: Mato Grosso; BA: Bahia; PE: Pernambuco; CE: Ceará; MS: Mato Grosso do Sul; AL: Alagoas; SC: Santa Catarina; BR: Brasília; GO: Goiás; SE: Sergipe; DF: Distrito Federal. Table 1 – Continuation. Impact of the use of pesticides by rural workers in Brazil 13 RBCIAMB | n.50 | dez 2018 | 1-25 da Educação). The majority of the articles are related to health disorders and occupational health, such as men- tal disorders, asthma, hearing, suicide, and poisoning. Reflecting the importance of agriculture to the coun- try’s economy, Brazil has a vast legislation specifically designed to regulate the stages of the agrochemicals’ life cycle at Federal and State level (GONÇALVES, 2016). All states have a pesticides register and authorization in their territory, but it also left some open controversial points regarding evaluation parameters and the attri- bution of inspection to the public power (GONÇALVES, 2016). Consequently, according to Pelaez, Terra and Sil- va (2010) there is a conflict of interests due to the ability of regulators, regulated companies and the companies themselves in adapting to the more stringent criteria for registering toxic substances (PELAEZ; TERRA; SILVA, 2010; GONÇALVES, 2016). There are studies that prove the contamination caused by the indiscriminate use of pesticides in different regions of Brazil (ALBUQUERQUE et al., 2016; CALDAS; ZANELLA; PRIMEL, 2011; RISSATO et al., 2007; LAABS et al., 2002; CALDAS et al., 1999; Laabs et al., 2002; ALHO; VIEIRA, 1997); however, this gap between Brazilian and state legislation leads to a panorama of uncertainties about the extent and de- gree of environmental contamination, as well as the dimension of effects to the human health and to the environment. Since there are no equal control proce- dures throughout the national territory, there are vul- nerabilities associated with the use of agrochemicals. The European Union, one of the world’s largest food producers and holding the position of the world’s larg- est wheat producer, is in the process of implementing the world’s most rigorous plan to reduce the use of pesticides. It culminated in the adoption of the Direc- tive 2009/128/CE on the sustainable use of pesticides, whose complete implementation is planned for 2020 (GONÇALVES, 2016). Health disorders and Occupational health As a result of the analysis of the selected articles, four thematic categories emerged, the first three being linked to the problems that the use or misuse of pesti- cides generate to the environment and human health and a category linked to the appropriate practices: • Health disorders and Occupational health; • Genotoxicity of pesticides; • Reproductive hormones and Sperm quality; • Practices to reduce exposure. Using AChE and BChE analysis, Oliveira-Silva et al. (2001), evaluated the exposures of rural workers of Rio de Janeiro State to anticholinesterasic pesticides. According to the authors’ results and to the enzymatic indicator used, data were distinct concerning the inci- dence of excessive exposure. In the studied sample, a result of 3.0% was found for BChE values, and 41.8% according to AChE. Individuals with at least one pos- itive enzymatic indicator result were considered as “intoxicated”. Considering these data and comparing them to the social-economic and pesticides use fac- tors, the importance of educational level in the preva- lence of intoxication was showed. The other indicators studied did not show any significant and evident cor- relation (OLIVEIRA-SILVA et al., 2001). In the same way, Pasiani et al. (2012) conducted a knowledge, attitudes, and practices (KAP)/biomonitoring study in an agricul- tural setting in Midwestern Brazil. For this purpose, they assessed the knowledge, attitudes, and practices regarding the use of pesticides by farmers in two rural settings and calculated the farmers and residents’ lev- els of exposure to organophosphorous and carbamate pesticides through red cells (AChE) and plasmatic bu- tyrilcholinesterase (BChE) analysis. In relation to these last analyses, for some farmers, the authors found higher activity of cholinesterase inhibition during the exposure period compared to what is considered safe. This may indicate that they might be at risk by the ex- posure to pesticides during their agricultural activities. AChE activity depletion was also found in family farm- ing settings, and thus may also be at risk from second- ary exposure to pesticides (PASIANI et al., 2012). From an epidemiological, clinical and laboratory aspects study of multiple exposure to pesticides in a represen- tative sample of 102 small farmers, Araújo et al. (2007), brought some light to moderate episodes of acute in- toxication by organophosphorates either described by the farmers or observed during clinical examination. Thirteen cases of delayed neuropathies were diag- Majolo, F.; Rempel, C. 14 RBCIAMB | n.50 | dez 2018 | 1-25 nosed and 29 cases of neural behavioral syndromes and psychiatric disorders associated to the continued use of pesticides. From these results, they found recur- rent multiple overexposures to high concentrations of different chemicals that may cause serious damage to vital functions, if considered their young age (average 35 ± 11 years old) and the productive period in their lifetime (ARAÚJO et al., 2007). Genotoxicity of pesticides The harmful effects on the health of rural workers, who are chronically exposed to mixtures of agrochemicals, are still little elucidated. In Brazil, Antonucci e Syllos (2000) found a positive relationship between genotox- icity and farmers in Parana, and Silva et al. (2008) in winery workers in Rio Grande do Sul, being observed chromosomal aberrations as genotoxicity markers ( SILVA, 2012). Among the most serious damage caused by pesticides, genotoxicity or genetic toxicology seeks to identify the action of agents that produce toxic and genotoxic ef- fects on the genetic material. From the interaction between our genetic material and genotoxic agents, the formation of adducts, oxidative alterations or even the breakdown of DNA molecules can happen (SILVA, 2012). The elimination of this cell or its repair by the organism usually occurs, however, if the lesion is fixed it will probably cause mutations, that is, hereditary al- terations. Thus, there will be a mutagenic effect, where during the replication process the perpetuation of the mutation in the daughter cells will take place (OBE et al., 2002; SILVA, 2012). The mutagenic potential is common between the pesti- cides, being extremely toxic to mammals. Because they inhibit the enzyme acetylcholinesterase, Organophos- phorus insecticides, for example, cause an accumu- lation of acetylcholine in nervous tissues, impairing neurotransmission. Therefore, a reaction with DNA molecules occurs, being able to generate substitutions of bases (GRISOLIA, 2005; SILVA, 2012). In 2006, the In- ternational Agency for Research on Cancer (IARC) came to consider the organophosphate Dichlorvos as possi- bly carcinogenic to man (SILVA, 2012). It is of vital importance to increase studies that seek the detection of cytogenetic damage caused by pesti- cides, since there is a strong association between occu- pational exposure to pesticides and different types of cancer (SILVA, 2012). Between them, we can highlight lung cancer (BEANE FREEMAN et al., 2005), bladder (VIEL; CHALLIER, 1995), pancreas (ANDREOTTI et al., 2009) and leukemias (BONNER et al., 2010) (SILVA, 2012). Mechanisms of action between mutagenesis and carcinogenesis may be related. As a consequence of the damage, the mutation may be the initial stage in the process by which most chemical carcinogens initi- ate tumor formation (RIBEIRO; SALVADORI; MARQUES, 2003; SILVA, 2012). Therefore, genotoxicity and muta- genicity assays for a given pesticide are important for cancer risk assessment. However, they do not have the capacity to predict their carcinogenic potential ( SILVA, 2012). Important and recent articles involving this area are from Tomiazzi et al. (2018), Hilgert Jacobsen-Pereira et al. (2018) and Silvério et al. (2017), performed in SP, SC and MG, respectively. In Tomiazzi et al. (2018), the authors study the relationship between the ex- posure to two xenobiotics with possible carcinogen- ic potential. In the exposed groups, the total number of cytogenetic abnormalities and MN were higher and the exposure to pesticides proved to be more deleterious than smoking. This finding is consistent with the exposure to a mixture of pesticides in the workplace, including compounds that are potential- ly carcinogenic in humans, as reported by pesticide group and smoking + pesticide group participants (TOMIAZZY et al., 2018). Results obtained by Hilgert Jacobsen-Pereira et al. (2018) indicate the presence of genotoxic and muta- genic effects in the exposed group. Continuous and low dose exposure to complex mixtures of pesticides is as- sociated to single and double strand breaks of DNA, ox- idative stress and crosslinks. It is important to highlight that DNA damage, when incorrectly or not repaired, can persist and accumulate, triggering mutagenic pro- cesses and causing important cytogenetic changes (BENEDETTI et al., 2013; HILGERT JACOBSEN-PEREIRA et al., 2018). From a study in southern Minas Gerais, Silvério et al. (2017) showed that workers had a hazardous exposure to organophosphates and afforded valuable data to es- Impact of the use of pesticides by rural workers in Brazil 15 RBCIAMB | n.50 | dez 2018 | 1-25 timate the risk to cancer development. The biomarkers used in this study are useful to assess and distinguish the occupational and environmental exposure to pesti- cides (SILVÉRIO et al., 2017). Reproductive hormones and Sperm quality It is interesting to highlight two studies approaching re- productive hormones and sperm quality (CREMONESE et al., 2017; FREIRE et al., 2014). Cremonese et al. (2017) investigated reproductive hormone levels, sperm qual- ity, and genital measures in rural compared to urban young men in the South of Brazil, examining their asso- ciation with occupational exposure to agricultural pesti- cides. According to their results, the main findings were: • the linear dose-response relationship’s poorer sperm morphology and life time use of all pesti- cides, fungicides, insecticides, herbicides, OP insec- ticides, dithiocarbamates and other chemical lass- es, mancozeb, glyphosate, and paraquat; • the association of lifetime use of pesticides, particu- larly herbicides and fungicides, with reduced levels of LH and prolactin; • the association of rural living and maternal farming during pregnancy with larger anogenital distance and testicular volume, but poorer sperm morphology. The authors suggest that chronic occupational ex- posure to modern pesticides, particularly herbicides and fungicides, may adversely affect semen quality in young male farmers in the South of Brazil, potential- ly leading to poorer morphology (CREMONESE et al., 2017). On the other hand, Freire et al. (2014) aimed to exam- ine the association between serum concentrations of organochlorine pesticides and levels of sex hormones in adult population in a rural area of Brazil heavi- ly contaminated with these pesticides. The authors found an inverse association between organochlorine pesticide concentrations and testosterone in men and LH and FSH in peri-/postmenopausal women, togeth- er with the high proportion of women with elevated prolactina. Based on their findings, the authors sug- gest that, in this population, these organochlorine compounds may have triggered anti-androgenic ef- fects in men and estrogenic effects in women (FREIRE et al., 2014). Practices to reduce exposure According to the World Health Organization, acciden- tal poisoning kills about 355,000 people every year. Two thirds of these deaths happen in developing coun- tries and are strongly associated with overexposure and inappropriate use of toxic chemicals, including pesticides (WHO, 2008; GONÇALVES, 2016). The use of pesticides has increased worldwide in the last decades, represent- ing a risk for several diseases in humans, including can- cer. As previously mentioned, genotoxicity underscores the importance of increasing studies that seek to detect cytogenetic damage caused by pesticides. It is among the most serious damage caused by pesticides, as there’s a strong association between occupational exposure to pesticides and different types of cancer. The inappropriate use of pesticides is of vital importance and is considered one of the main public health problems, mainly in the interior of Brazil. There are few, however, valuable studies related to the characteristics of their oc- cupational use in order to identify the effects of the ag- rochemicals’ use by rural workers from basic science with enough relevance to give a return to society’s health. Therefore, it is necessary to obtain a profile of the rural worker through the study on the use of agrochemicals’ impact, as well as the possible genetic and cytological modifications that can be triggered by these treatments. According to Abreu & Alonzo (2014), the chemical indus- tries encourage the expansion of the use of their prod- ucts through aggressive marketing and commercializa- tion practices, supported by the Brazilian legislation on agrochemicals (PORTO & SOARES, 2012; MIRANDA et al., 2007). They disregard the health impacts on farm- ers by promoting “safe use” (ABREU & ALONZO, 2014). The safety manuals prepared by the Associação Nacio- nal de Defesa Vegetal (IWAMI et al., 2010; ASSOCIAÇÃO NACIONAL DE DEFESA VEGETAL, 2006) credit the haz- ards and accidents involved in the handling of pesticides to the “incorrect use” by the worker and not to the tox- icity of the formulations and to the imposition of the ag- rochemical model of production in the Country (BREIHL, 2003; ABREU & ALONZO, 2014). Majolo, F.; Rempel, C. 16 RBCIAMB | n.50 | dez 2018 | 1-25 Quite common for rural workers, mainly by poor commu- nication of risks to the population, is mixing active sub- stances with the objective of achieving a potent effect, the so-called cocktail effect (REFFSTRUP; LARSEN; MEY- ER, 2010; HERNÁNDEZ et al., 2013; GONÇALVES, 2016). Individually, these active substances can be approved but mixed imply greater risks. Brazilian legislation does not provide tests on the effects of that, which are frequent and rarely punished. Although already regulated in sever- al States, there is an urgent need to spread the informa- tion about the risks of using agrochemicals to the popu- lation and gain national dimension (GONÇALVES, 2016). Stoppelli & Magalhães (2005), cited some strategies to minimize negative impacts to the producer and con- sumer: greater inspection of manufacturing, import, export and quality, as well as products sales; greater control over use, including correct disposal of empty packaging and waste; application only when necessary, in the correct dose and preferring less toxic formula- tions; greater control in commercialized foods; restric- tions by the responsible organs of those products with- out full epidemiological and environmental studies; banning, when necessary, classes of pesticides; simpli- fying labels on packaging; risk communication; changes in the production and labor model; greater adequacy of protective equipment to excessive heat in tropical countries. Also incentive to government policies that incorporate, before crediting these products, an earlier structuring of the system, such as the preparation of labor, certification of Good Agricultural Practices and compliance with laws and improvements in inspection (STOPPELLI & MAGALHÃES, 2005). As reported by Maroni, Fait and Colosio (1999), in the European Union a set of tests is required and designed to identify a toxicological profile of the substance. This profile includes: acute toxicity (oral, inhalation, dermal), skin and eye irritation, skin sensi- tization, short-term toxicity (28–90 days), mutagenic- ity, long-term toxicity (2 years), carcinogenicity, repro- ductive toxicity and other special effects (MARONI; FAIT; COLOSIO, 1999). According to the same author, developed countries’ stringent requirements have to be satisfied before a product is authorized and the costs of meeting these requirements are very high. With the lack of legislation and adequate control’s infrastructure to enforce legislation mainly in devel- oping countries, the rural worker, often misinformed, starts to use pesticides that contain dangerous com- pounds which do not have controlled adverse effects both to humans and to the environment (MARONI; FAIT; COLOSIO, 1999). The production of organic products through price re- duction policies is also worth highlighting as a possible measure to be taken. According to Soares (2010), as it is done with alcohol and cigarettes in Brazil, making the production of pesticides less attractive by charging the products with high toxicity could be done. Having less than 1% of accredited establishments, the organ- ic market in Brazil is considered very shy (IBGE, 2006; SOARES, 2010). Already in Europe, mainly due to the implemented policies encouraged the expansion of this market. About 11% of the land used for agriculture in Austria is occupied by certified organic producers, 7 to 10% in the Czech Republic, Greece, Italy, Sweden and Switzerland, 4 to 6% in Denmark, Estonia, Ger- many, Finland, Lithuania, Portugal, Slovakia, Slovenia, Spain and the United Kingdom, and less than 3% in oth- er countries (PADEL; RÖCKLINSBERG; SCHMID, 2009; SOARES, 2010). CONCLUSION Rural workers and planting care are associated with a variety of occupational health hazards, both by physical factors and extreme weather conditions, and by exposure to hazards arising from the use of toxicological chemicals, such as pesticides and fertil- izers. There are also biological and mechanical risks. Farmers are involved in different farming activities, so they are susceptible to numerous work-related health disorders. In many cases, producers do not give adequate attention to preventing and controlling occupational health problems. For the rural environ- ment, comprehensive occupational health programs are adequately developed for this public, involving both preventive, curative and rehabilitation aspects. Studies such as Chaudhuri (2000), Cavalheiro et al. (2014) and Rempel, Haetinger and Sehnem (2013) demonstrate that there are health problems relat- ed to the occupational health of rural producers and that they demonstrate that specific programs can im- prove their quality of life. Impact of the use of pesticides by rural workers in Brazil 17 RBCIAMB | n.50 | dez 2018 | 1-25 Several studies report and describe the genotoxic effect of pesticides on farmers who use them, including a study by Doğanlar et al. (2018), which shows that populations of areas close to sites that use agrotoxic, even if they are not in contact with them, present an increase in the geno- toxicity verified in blood test. These same authors sug- gest that biological monitoring efforts should be made to control non-occupational exposure to pesticides and thus safeguarding the health of agricultural residents. Despite the possible immediate benefits of using pesti- cides, it is important to stress that they are toxic substanc- es and that their uncontrolled use causes severe damage to environmental and human health (GONÇALVES, 2016). Many countries encourage sustainable agricultural prac- tices and have restrictions on importing products with- out proven food security. Therefore, even if the elimina- tion of pesticide use in agriculture is still far away, its use in a rational manner and respecting quantity, application, environmental legislation and with appropriate PPE use, make the genotoxic risks smaller. Most articles that relate the change in reproductive hormones and sperm quality to the prolonged use of pesticides in agriculture also mention that pregnant women exposed to pesticides accumulate active ingre- dients and pass them to the fetus. In a study carried out with rural producers in a city in the interior of Rio Grande do Sul, they do not relate the inadequate use of pesticides to their health status, even though they know the problems that pesticides can have on their health (WAHLBRINCK; BICA; REMPEL, 2017). Many countries, mainly from the European Union, have adopted targets to reduce the use of agrochemicals, but countries that have their agriculture heavily depen- dent on pesticides must follow the regulations of the US EPA, which is the agency that regulates the amount of pesticide residues considered to be reliable in food. These sustainable environmental measures and practic- es, such as crop rotation and crop diversity, are neces- sary to ensure that even using only pesticides, there is less risk of generating health problems. Also, the mea- sures adopted by the EU can be adapted to the Brazilian reality, improving the Brazilian agrochemicals’ manage- ment system and for the Brazilian products to be certi- fied and accepted in the European market. This review made it possible to understand the current situation of the association between the exposure to pesticides and their possible effects caused to Brazil- ian rural workers. Considering the size of the country and although the research on the impact of the use of pesticides on human health has grown in recent years, it is still insufficient to really know the dimension of their damage on human health, caused by occupation- al exposure and by the intensive use of agrochemicals. It is fundamental to identify the presence of genotoxic and mutagenic effects of the use of pesticides in rural workers, considering the strong relationship between mutagenesis and carcinogenesis in pesticide users, as well as other damages involving health disorders and reproductive hormones. Brazil has been growing in relation to the consumption of agrochemicals as well as in the production and ex- port of agricultural products. It is up to us, and mainly to the governments, the search for the disciplining of their use, preventive actions and change to an agricul- ture aware of the environmental health, the consumer and the rural worker (STOPPELLI & MAGALHÃES, 2005). CONFLICT OF INTERESTS The authors confirm that this article content has no conflicts of interest. FUNDING SOURCES This study was financed in part by the Brazilian Coor- dination for the Improvement of Higher Education Per- sonnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES), Finance Code 001. 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